TUMOR GROWTH AND METASTASIS IN TRIPLE NEGATIVE BREAST CANCER

Abstract

Triple negative breast cancer remains a poorly understood clinical subtype of breast cancer associated with increased aggression, limited treatment options, and ultimately, worsened patient outcomes. Cancer progression can be divided conceptually into two main phases: primary tumorigenesis, the critical initial phase which requires numerous cellular aberrations, and secondary metastasis, the later phase where cancer cells gain additional mutations that enable dissemination from an established tumor and colonization of disparate tissue sites in the body. In Part I of this thesis, the role of diabetic hyperglycemia in triple negative breast cancer primary tumor growth in the context of non-enzymatic glycation is investigated. While it is well established that Type II diabetes mellitus is associated with increased incidence and severity of numerous comorbidities including triple negative breast cancer, there has been little work done to elucidate the nature of these disease interactions. This work delineates a novel role for diabetic hyperglycemia-mediated non-enzymatic glycation due in increased triple negative breast cancer tumor growth. In Part II of this thesis, the metastatic potentials of highly migratory and weakly migratory subpopulations of triple negative breast cancer cells are compared. Contrary to the common paradigm in cancer migration research that adoption of a migratory phenotype is associated with metastatic ability, we found that the weakly migratory subpopulation was highly metastatic in an E-cadherin dependent manner compared to weakly metastatic, highly migratory subpopulation. This work highlights the importance of parsing apart intratumor heterogeneity and indicates that migratory ability is not always correlated with metastatic potential.